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ONITT: Study of Onivyde with Talazoparib or Temozolomide in Children and Young Adults with Recurrent/Refractory Solid Tumors and Ewing Sarcoma

Phase 1/2 Study of Onivyde in combination with Talazoparib or Temozolomide in Children and Young Adults with Recurrent/Refractory Solid Tumors and Ewing Sarcoma

Categories:

Solid Tumor

Phase I/II

Diseases Treated:

Solid tumors
Ewing sarcoma

Eligibility Overview:

  • Ages 12 months old to 30 years
  • Diagnosed with recurrent or refractory solid tumor (Phase 1)
  • Diagnosed with recurrent or refractory Ewing sarcoma (Phase 2)
  1. This is a phase 1/2 study to evaluate onivyde plus talazoparib or temozolomide in pediatric patients with recurrent/refractory solid tumors and Ewing sarcoma.

    Onivyde is irinotecan that has been encapsulated into a liposomal drug delivery system to increase intratumoral drug exposure while decreasing system toxicities. Talazoparib is a highly potent, orally bioavailable small molecule inhibitor of PARP1 and 2 and has significant activity in cancer cell lines with DNA damage repair deficiencies. In vitro and in vivo studies of PARP inhibitors with or without chemotherapy demonstrated significant activity against Ewing sarcoma.

    In phase 1 of this study, patients with recurrent/refractory solid tumors will be randomized to Arm A (onivyde plus talzaoparib) or Arm B (onivyde plus temozolomide). Once the recommended phase 2 doses are determined, expansion cohorts will open for enrollment of non-Ewing sarcoma solid tumor patients. Concurrently, the phase 2 study will open to patients with recurrent/refractory Ewing sarcoma. Patients in phase 2 will be randomized to receive one of the two regimens.

    Primary Objective

    • Phase 1: To determine the recommended phase 2 doses of onivyde combined with talazoparib (Arm A) and onivyde combined with temozolomide (Arm B) in children, adolescents and young adults with refractory or recurrent solid tumors
    • Phase 2: To compare the progression-free survival of onivyde plus talazoparib and onivyde plus temozolomide in patients with refractory or recurrent Ewing sarcoma

    Eligibility Criteria

    Inclusion criteria include:

    • At least 12 months old and 30 years or younger
    • Diagnosed with recurrent or refractory non-central nervous system (CNS) solid tumors (Phase 1)
    • Diagnosed with recurrent or refractory Ewing sarcoma (during or after completion of first-line therapy) with EWSR1-FLI1 translocation or other EWS rearrangement (Phase 2)
    • Adequate organ and bone marrow function

    Exclusion Criteria include:

    • Pregnant or breastfeeding
    • Use of other investigational drugs while on the study
    • Treatment within last 7 days prior to enrollment with food or drugs known to be strong CYP3A4 inhibitors
    • Treatment within last 7 days prior to enrollment with drugs known to be strong CYP3A4 inducers
    • Treatment within last 7 days prior to enrollment with drugs known to be potent P-gp inhibitors
    • Previous treatment with talazoparib or onivyde (Phase 1)
    • Progression on a PARP inhibitor plus irinotecan-containing regimen
    • Previous treatment with talazoparib, onivyde or temozolomide (Phase 2)

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in and outside the U.S.

  2. About this study

    This is a research study of a drug called onivyde  (liposomal irinotecan) in combination with the drugs talazoparib or temozolomide. All three drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers. The treatment in this study is considered experimental because it has not been proven to work in children and young adults with solid tumors or Ewing sarcoma. We are studying this combination because it seems to work against cancer in the laboratory and animals. This combination has not been tested in children.

    If you are accepted to this study, you or your child will receive one of two treatments:

    1. Onivyde + Talazoparib (Arm A), or
    2. Onivyde + Temozolomide (Arm B)

    Because there is not much information about this treatment’s effect on cancers in humans, we do not know if you will benefit from taking part in this study. However, what we learn from this study may help future patients with cancer.

    Purpose of this clinical trial

    The main goal of this study is to test new experimental drugs in hopes of finding a treatment that may work against tumors that have come back or that have not responded to standard therapy in children, adolescents and young adults.

    Eligibility overview

    • At least 12 months old and 30 years or younger
    • Diagnosed with recurrent or refractory solid tumor (Phase 1)
    • Diagnosed with recurrent or refractory Ewing sarcoma (Phase 2)
  3. ONITT
    Sponsors: St. Jude Children’s Research Hospital
    ClinicalTrials.gov identifier

    NCT04901702

    Trial Start Date: May 2021
    Estimated Enrollment: 70
    Study Type: Interventional
    Study Phase: Phase I /2
    Conditions: Solid turmor, Ewing sarcoma
    Ages: 1 to 30 years old
    Principal investigator: Sara Federico, MD
    Study Sites: St. Jude Children’s Research Hospital and collaborating sites outside the U.S.
    For a consultation or to discuss ONITT: St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.